The Role of miR-310s in Regulation of Somatic Cell Differentiation in Drosophila Ovary. Omer Cicek, Halyna Shcherbata. MPRG of Gene Expression and Signaling, Max Planck Institute, Goettingen, Germany.

   miRNAs are short noncoding RNA molecules, which have regulatory roles in gene expression and which have been shown to act on diverse cellular and physiological processes such as cell survival, death, and fate determination. Among many fine-tuned homeostases throughout the body, continuous generation of adult tissues from their respective adult stem cells is tightly regulated. Stem cell divides asymmetrically into another stem cell and a daughter that undergoes differentiation. An open question of great importance is how stem cell progeny determines appropriate cell fate. Problems in cell specification can result in permanent loss of regenerative tissue or excessive cancerous overproliferation. We use the Drosophila ovary as a model system to study the specificity of cell differentiation, since ovarian soma bears different types of cells; for example, terminal filament and cap cells are mitotically inactive, while follicular epithelium and stalk cells are constantly replenished by follicle stem cell division. Stalk cells are terminally differentiated, while follicle cells undergo mitotic and endomitotic cell division. Our data show the role of the recently evolved miR-310s complex that consists of miR-310, 311, 312, and 313 in the process of regulation of somatic cell fate in the Drosophila ovary. This miRNA complex is expressed in terminally differentiated stalk cells. The deletion of miR-310s results in multilayered epithelial phenotypes that are enhanced due to stress conditions. We found that Rab23, a negative regulator of highly evolutionary conserved Hedgehog (Hh) pathway that has been shown to determine cell fate in the ovary, is a miR-310s target in somatic cells. Taken together, our data show that cell specification can be adjusted by miRNAs in response to external conditions: miR-310s fine tune the strength of Hh signaling that in turn regulates cell fate determination.